Genetic Variant INHBB:p.His208His (chr2-120349274-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002193.4(INHBB):c.624C>T(p.His208His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0557 in 1,614,078 control chromosomes in the GnomAD database, including 5,989 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.065 ( 762 hom., cov: 33)

Exomes 𝑓: 0.055 ( 5227 hom. )

Consequence

INHBB
NM_002193.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.884

Publications

13 publications found

Variant links:

Genes affected

INHBB (HGNC:6067): (inhibin subunit beta B) This gene encodes a member of the TGF-beta (transforming growth factor-beta) superfamily of proteins. The encoded preproprotein is proteolytically processed to generate a subunit of the dimeric activin and inhibin protein complexes. These complexes activate and inhibit, respectively, follicle stimulating hormone secretion from the pituitary gland. Polymorphisms near this gene are associated with pre-eclampsia in female human patients. [provided by RefSeq, Aug 2016]

INHBB links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP7

Synonymous conserved (PhyloP=-0.884 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INHBB	NM_002193.4 link	c.624C>T	p.His208His	synonymous_variant	Exon 2 of 2	ENST00000295228.4	NP_002184.2	P09529

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INHBB	ENST00000295228.4 link	c.624C>T	p.His208His	synonymous_variant	Exon 2 of 2	1	NM_002193.4	ENSP00000295228.3		P09529

Frequencies

GnomAD3 genomes

AF:

0.0653

AC:

9936

AN:

152096

Hom.:

757

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0482

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.150

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.393

Gnomad SAS

AF:

0.0589

Gnomad FIN

AF:

0.0657

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0363

Gnomad OTH

AF:

0.0556

GnomAD2 exomes

AF:

0.0901

AC:

22649

AN:

251440

AF XY:

0.0819

show subpopulations

Gnomad AFR exome

AF:

0.0500

Gnomad AMR exome

AF:

0.198

Gnomad ASJ exome

AF:

0.0109

Gnomad EAS exome

AF:

0.409

Gnomad FIN exome

AF:

0.0645

Gnomad NFE exome

AF:

0.0354

Gnomad OTH exome

AF:

0.0668

GnomAD4 exome

AF:

0.0547

AC:

79942

AN:

1461864

Hom.:

5227

Cov.:

AF XY:

0.0536

AC XY:

39008

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.0448

AC:

1499

AN:

33480

American (AMR)

AF:

0.194

AC:

8682

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0117

AC:

305

AN:

26136

East Asian (EAS)

AF:

0.383

AC:

15195

AN:

39700

South Asian (SAS)

AF:

0.0518

AC:

4464

AN:

86258

European-Finnish (FIN)

AF:

0.0605

AC:

3229

AN:

53396

Middle Eastern (MID)

AF:

0.0316

AC:

182

AN:

5768

European-Non Finnish (NFE)

AF:

0.0383

AC:

42593

AN:

1112008

Other (OTH)

AF:

0.0628

AC:

3793

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

4783

9565

14348

19130

23913

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1910

3820

5730

7640

9550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0653

AC:

9946

AN:

152214

Hom.:

762

Cov.:

AF XY:

0.0708

AC XY:

5268

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0481

AC:

1999

AN:

41550

American (AMR)

AF:

0.150

AC:

2293

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0107

AC:

AN:

3472

East Asian (EAS)

AF:

0.394

AC:

2031

AN:

5152

South Asian (SAS)

AF:

0.0589

AC:

284

AN:

4818

European-Finnish (FIN)

AF:

0.0657

AC:

696

AN:

10600

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0363

AC:

2470

AN:

68016

Other (OTH)

AF:

0.0588

AC:

124

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

422

845

1267

1690

2112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0544

Hom.:

389

Bravo

AF:

0.0753

Asia WGS

AF:

0.189

AC:

657

AN:

3478

EpiCase

AF:

0.0333

EpiControl

AF:

0.0327

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.5

(source)

DANN

Benign

0.91

PhyloP100

-0.88

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over